ArticleGenes & development2016
MMP-9 facilitates selective proteolysis of the histone H3 tail at genes necessary for proficient osteoclastogenesis.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
75 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.
- Bone mineral density loci specific to the skull portray potential pleiotropic effects on craniosynostosis.Communications biology · 2023Pooled it
- Life-Course Genome-wide Association Study Meta-analysis of Total Body BMD and Assessment of Age-Specific Effects.American journal of human genetics · 2018Pooled it
- Identification of Hip BMD Loss and Fracture Risk Markers Through Population-Based Serum Proteomics.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Trial
- B1486 is a highly potent VprBP inhibitor capable of blocking osteoclast differentiation and bone resorption.The Journal of biological chemistry · 2026Article
- A peroxiredoxin 1-reactive oxygen species feedback loop modulates nuclear factor kappa B activity in osteoclastogenesis.Molecular biomedicine · 2026Article
- Cleavage of histone H2A during embryonic stem cell differentiation destabilizes nucleosomes to counteract gene activation.The Journal of biological chemistry · 2026Article
- VprBP drives prostate tumorigenesis by its kinase activity targeting histone H2A.Cell communication and signaling : CCS · 2026Article
- HDAC1 has intrinsic protease activity and regulates transcription through clipping histone H3 N-terminal tail.Cell death and differentiation · 2026Article
- Hypoxia Preserves Chromatin Integrity and Delays Cellular Senescence through Epigenetic Regulation.Biomolecules & therapeutics · 2026Review
- Cell-penetrating H3 tail peptides suppress osteoclast differentiation via inhibition of MMP-9-mediated histone H3 clipping.BMB reports · 2026Article
- MMP-3 cleavage of Lamin A induces pro-migratory nuclear deformity, nucleophagy, and their autophagic secretion with extracellular vesicles in metastatic cancer.Cell communication and signaling : CCS · 2026Article
- Decoding Epigenetic Switches: How Histone Acetylation/Deacetylation Regulates Mononuclear/Macrophage Fate in Bone Disorders.International journal of biological sciences · 2026Review
- Epigenetic drivers of metalloproteinases and metastasis.Trends in cell biology · 2025Review
- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
- Developmental Endothelial Locus-1 Promotes Osteoclast Differentiation and Activation.International journal of molecular sciences · 2025Article
- Leveraging Zymography to Discover and Investigate Nuclear Proteases.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- Denatonium inhibits RANKL-induced osteoclast differentiation and rescues the osteoporotic phenotype by blocking p65 signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- VprBP regulates osteoclast differentiation via an epigenetic mechanism involving histone H2A phosphorylation.Epigenetics & chromatin · 2024Article
- Histone Tail Cleavage as a Mechanism for Epigenetic Regulation.International journal of molecular sciences · 2024Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Although limited proteolysis of the histone H3 N-terminal tail (H3NT) is frequently observed during mammalian differentiation, the specific genomic sites targeted for H3NT proteolysis and the functional significance of H3NT cleavage remain largely unknown. Here we report the first method to identify and examine H3NT-cleaved regions in mammals, called chromatin immunoprecipitation (ChIP) of acetylated chromatin (ChIPac). By applying ChIPac combined with deep sequencing (ChIPac-seq) to an established cell model of osteoclast differentiation, we discovered that H3NT proteolysis is selectively targeted near transcription start sites of a small group of genes and that most H3NT-cleaved genes displayed significant expression changes during osteoclastogenesis. We also discovered that the principal H3NT protease of osteoclastogenesis is matrix metalloproteinase 9 (MMP-9). In contrast to other known H3NT proteases, MMP-9 primarily cleaved H3K18-Q19 in vitro and in cells. Furthermore, our results support CBP/p300-mediated acetylation of H3K18 as a central regulator of MMP-9 H3NT protease activity both in vitro and at H3NT cleavage sites during osteoclastogenesis. Importantly, we found that abrogation of H3NT proteolysis impaired osteoclastogenic gene activation concomitant with defective osteoclast differentiation. Our collective results support the necessity of MMP-9-dependent H3NT proteolysis in regulating gene pathways required for proficient osteoclastogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.